Manuguerra was born in Tunis, Tunisia, to Italian parents, who later moved to Argentina.
After singing widely in Europe, Manuguerra made his American debut in 1968, as Gérard in Andrea Chénier, in Seattle.
He made his Metropolitan Opera debut on 11 January 1971 as Enrico in Lucia di Lammermoor, other roles included Barnaba in La Gioconda, Carlo in La forza del destino, Amonasro in Aida, Alfio in Cavalleria rusticana, Tonio in Pagliacci, and others.
Manuguerra had a rich and supple voice enabling him to excel in both belcanto and verismo repertoire, with Verdi being always at the core, which his impressive discography clearly demonstrates.
Matteo Manuguerra enjoyed a long career and was still active when he died suddenly of a heart attack, in Montpellier, France.